Abstract
Both hyperoxia-induced proapoptotic sensitization of alveolar type II cells (TII cells) and high-stretch mechanical ventilation induced pulmonary inflammation are tumor necrosis factor alpha (TNFα) mediated. Therefore, binding of free TNFα should protect from TNFα-mediated acute lung injury and ameliorate the subsequently developing chronic lung disease. Here, the authors show that a single subcutaneous pretreatment of rat with etanercept, a recombinant p75 TNF receptor 2 human immunoglobulin G1 (IgG1) construct, inhibits the hyperoxia-induced and TNFα-mediated increase in the expression of TNFα receptor, the activation of caspase 3 in TII cells, and, as an early indicator of lung injury, the capillary-alveolar leakage and granulocyte number in lung lavage. The authors assume that subcutaneous administration of etanercept might be suitable to prevent acute lung injury and its sequelae induced by hyperoxic ventilation of premature neonates and critically ill patients.
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